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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well described and conducted study with very little deviations from the OECD guidelines
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
low frequency of body weight measurement, only one third of the litters examined for soft-tissues examination
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): vinylidene chloride
- Substance type: production grade
- Physical state: liquid
- Analytical purity: 99.5 %
- Impurities (identity and concentrations): monomethylether of hydroquinone (MEHQ) / residual concentration : 1-5 mg/L
- Source: The Dow Chemical Company, Midland, Mich.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Spartan Research Animals, Inc., Haslett, Mich.
- Weight at study initiation: 250 g
- Housing: housed individually in wire-bottom cages
- Diet: commercial laboratory animal chow (Ralston Purina Co., St. Louis, Mo.) ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
- Rate of preparation of diet (frequency): daily
- Concentration in vehicle: 200 mg/L
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
No data
Details on mating procedure:
The day on which sperm were found in the vaginal smear of rats was considered as day 0 of pregnancy.
Duration of treatment / exposure:
10 days : from day 6 to day 15 of gestation
Frequency of treatment:
ad libitum
Duration of test:
Until day 21 of gestation
No. of animals per sex per dose:
24 rats for control
26 rats for 200 mg/L group
Control animals:
yes, concurrent vehicle
Details on study design:
No data

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations not included.

Time schedule for body weight examinations: days 6, 10, 16 and 21 of gestation
Water consumption for each animal determined every 3 days or less and exposure calculated as g vinylidene chloride/kg body weight/day

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: weight of maternal liver
Ovaries and uterine content:
The uteri of nonpregnant animals were stained with a 10 % solution of sodium sulfide and examined for evidence of early resorption sites (Kopf et al., 1964)
The number and position of live, dead, and resorbed fetuses were noted
Fetal examinations:
After being weighed, measured (crown-rump length), and the sexes noted, all fetuses were examined for external alterations and cleft palate. One-third of the fetuses from each litter, selected at random, was examined immediately for evidence of soft-tissue alterations by dissection under a stereomicroscope (Staples, 1974). The head of each rat fetus which was examined for soft-tissue alterations was placed in Bouin's solution and subsequently examined by the razor section technique of Wilson (1965). All fetuses were cleared with KOH, stained with alizarin red-S (Dawson, 1926), and examined for skeletal alterations.
Statistics:
The incidence of pregnancy was analyzed by the Fisher exact probability test (Siegel, 1956).
The Wilcoxon test as modified by Haseman and Hoel (1974) was used to evaluate the incidence of fetal alterations.
Fetal body weights and body measurements, maternal body and liver weights, and food and water consumption data were analyzed by a one-way analysis of variance (Steel and Torrie, 1960). The level of significance reported was p< 0.05.
Indices:
No data
Historical control data:
No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No test dams died. No change in food and water consumption was noted. No alteration of liver weight.
The incidence of pregnancy was not significantly altered by exposure to 1,1-dichloroethene.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Statistically significant increase in the average number of corpora lutea per dam (mean ± SD : 12 ± 2 vs. 14 ± 3 for control vs. 1,1-dichloroethene group, respectively)
The mean fetal crown-rump length was significantly greater than that of the controls (Mean of the litter means ± SD : 46.6 ± 2.4 vs. 47.8 ± 1.3 mm for control vs. vinylidene chloride group, respectively)
No significant effect on the average number of implantations, live fetuses, resorptions, sex ratio or body weight
Neither skeletal alteration nor major malformations was significantly different from the controls

Effect levels (fetuses)

Remarks on result:
other: not specified
Remarks:
not specified

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No evidence of toxicity to the dams or their offspring
NOAEL = 200 mg/L = 40 mg/kg bw/day
Executive summary:

The teratogenic effect of 1,1-dichloroethene was assessed on Sprague-Dawley pregnant rats given 200 mg/L of 1,1-dichloroethene in drinking-water (equivalent to 40 mg/kg/day) from day 6 to day 15 of gestation. No evidence of toxicity to the dams or their offspring was observed.